WO2019200124A1 - Molécules d'inhibiteur d'acide nucléique double brin modifiées avec des nucléotides augmentant tm - Google Patents

Molécules d'inhibiteur d'acide nucléique double brin modifiées avec des nucléotides augmentant tm Download PDF

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Publication number
WO2019200124A1
WO2019200124A1 PCT/US2019/027021 US2019027021W WO2019200124A1 WO 2019200124 A1 WO2019200124 A1 WO 2019200124A1 US 2019027021 W US2019027021 W US 2019027021W WO 2019200124 A1 WO2019200124 A1 WO 2019200124A1
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WIPO (PCT)
Prior art keywords
nucleic acid
double
acid inhibitor
nucleotides
nucleotide
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PCT/US2019/027021
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English (en)
Inventor
Weimin Wang
Naim NAZEF
Bob Dale Brown
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Dicerna Pharmaceuticals, Inc.
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Publication date
Application filed by Dicerna Pharmaceuticals, Inc. filed Critical Dicerna Pharmaceuticals, Inc.
Priority to CN201980025615.0A priority Critical patent/CN111971051A/zh
Priority to JP2020554092A priority patent/JP2021520355A/ja
Priority to MX2020010802A priority patent/MX2020010802A/es
Priority to KR1020207029911A priority patent/KR20200144100A/ko
Priority to AU2019252529A priority patent/AU2019252529A1/en
Priority to CA3094008A priority patent/CA3094008A1/fr
Priority to EP19784831.0A priority patent/EP3773609A4/fr
Publication of WO2019200124A1 publication Critical patent/WO2019200124A1/fr
Priority to IL277813A priority patent/IL277813A/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/111—General methods applicable to biologically active non-coding nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering N.A.
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/322—2'-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3519—Fusion with another nucleic acid
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/50—Physical structure
    • C12N2310/52—Physical structure branched
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/50—Physical structure
    • C12N2310/53—Physical structure partially self-complementary or closed
    • C12N2310/531—Stem-loop; Hairpin
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/50—Physical structure
    • C12N2310/53—Physical structure partially self-complementary or closed
    • C12N2310/533—Physical structure partially self-complementary or closed having a mismatch or nick in at least one of the strands
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/50—Methods for regulating/modulating their activity
    • C12N2320/52—Methods for regulating/modulating their activity modulating the physical stability, e.g. GC-content
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y102/00—Oxidoreductases acting on the aldehyde or oxo group of donors (1.2)
    • C12Y102/01—Oxidoreductases acting on the aldehyde or oxo group of donors (1.2) with NAD+ or NADP+ as acceptor (1.2.1)
    • C12Y102/01003—Aldehyde dehydrogenase (NAD+) (1.2.1.3)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21—Serine endopeptidases (3.4.21)
    • C12Y304/21061—Kexin (3.4.21.61), i.e. proprotein convertase subtilisin/kexin type 9

Abstract

L'invention concerne des molécules d'inhibiteur d'acide nucléique double brin ayant un brin sens avec une structure tige boucle et un brin antisens, la partie de tige de la structure tige boucle contenant un ou plusieurs nucléotides augmentant Tm. L'invention concerne également des procédés et des compositions pour réduire l'expression du gène cible et des procédés et des compositions pour traiter une maladie d'intérêt.
PCT/US2019/027021 2018-04-13 2019-04-11 Molécules d'inhibiteur d'acide nucléique double brin modifiées avec des nucléotides augmentant tm WO2019200124A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
CN201980025615.0A CN111971051A (zh) 2018-04-13 2019-04-11 用增加tm的核苷酸修饰的双链核酸抑制剂分子
JP2020554092A JP2021520355A (ja) 2018-04-13 2019-04-11 Ｔｍ上昇ヌクレオチドで修飾された二本鎖核酸阻害剤分子
MX2020010802A MX2020010802A (es) 2018-04-13 2019-04-11 Moleculas inhibidoras de acidos nucleicos de caracter bicatenario modificadas con nucleotidos que aumentan la tm.
KR1020207029911A KR20200144100A (ko) 2018-04-13 2019-04-11 Tm-증가 뉴클레오타이드로 변형된 이중-가닥 핵산 억제제 분자
AU2019252529A AU2019252529A1 (en) 2018-04-13 2019-04-11 Double-stranded nucleic acid inhibitor molecules modified with Tm-increasing nucleotides
CA3094008A CA3094008A1 (fr) 2018-04-13 2019-04-11 Molecules d'inhibiteur d'acide nucleique double brin modifiees avec des nucleotides augmentant tm
EP19784831.0A EP3773609A4 (fr) 2018-04-13 2019-04-11 MOLÉCULES D'INHIBITEUR D'ACIDE NUCLÉIQUE DOUBLE BRIN MODIFIÉES AVEC DES NUCLÉOTIDES AUGMENTANT Tm
IL277813A IL277813A (en) 2018-04-13 2020-10-05 Tm-enhanced double-helix nucleic acid tracer molecules with nucleotides

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201862657428P 2018-04-13 2018-04-13
US62/657,428 2018-04-13
US201862778755P 2018-12-12 2018-12-12
US62/778,755 2018-12-12

Publications (1)

Publication Number Publication Date
WO2019200124A1 true WO2019200124A1 (fr) 2019-10-17

Family

ID=68161339

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2019/027021 WO2019200124A1 (fr) 2018-04-13 2019-04-11 Molécules d'inhibiteur d'acide nucléique double brin modifiées avec des nucléotides augmentant tm

Country Status (10)

Country Link
US (1) US11873488B2 (fr)
EP (1) EP3773609A4 (fr)
JP (1) JP2021520355A (fr)
KR (1) KR20200144100A (fr)
CN (1) CN111971051A (fr)
AU (1) AU2019252529A1 (fr)
CA (1) CA3094008A1 (fr)
IL (1) IL277813A (fr)
MX (1) MX2020010802A (fr)
WO (1) WO2019200124A1 (fr)

Cited By (2)

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Publication number Priority date Publication date Assignee Title
WO2020226960A1 (fr) * 2019-05-03 2020-11-12 Dicerna Pharmaceuticals, Inc. Molécules d'inhibiteur d'acide nucléique double brin à brins sens raccourcis
EP3894560A4 (fr) * 2018-12-12 2022-10-19 Dicerna Pharmaceuticals, Inc. Molécules d'inhibiteur d'acide nucléique double brin contenant une triboucle

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WO2023069707A2 (fr) * 2021-10-22 2023-04-27 Sirnaomics, Inc. Produits et compositions
WO2023176863A1 (fr) * 2022-03-16 2023-09-21 第一三共株式会社 Oligonucléotide chimiquement modifié ayant une activité d'arni

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Cited By (2)

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Publication number Priority date Publication date Assignee Title
EP3894560A4 (fr) * 2018-12-12 2022-10-19 Dicerna Pharmaceuticals, Inc. Molécules d'inhibiteur d'acide nucléique double brin contenant une triboucle
WO2020226960A1 (fr) * 2019-05-03 2020-11-12 Dicerna Pharmaceuticals, Inc. Molécules d'inhibiteur d'acide nucléique double brin à brins sens raccourcis

Also Published As

Publication number Publication date
EP3773609A1 (fr) 2021-02-17
JP2021520355A (ja) 2021-08-19
IL277813A (en) 2020-11-30
CA3094008A1 (fr) 2019-10-17
KR20200144100A (ko) 2020-12-28
AU2019252529A1 (en) 2020-10-01
EP3773609A4 (fr) 2022-05-18
CN111971051A (zh) 2020-11-20
MX2020010802A (es) 2020-10-28
US20190316125A1 (en) 2019-10-17
US11873488B2 (en) 2024-01-16

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